The overall goal of this project is to develop MR imaging methods to identify the biochemical components and biophysical characteristics of atherosclerotic plaques in vitro and in vivo This will be accomplished through the mapping of the heterogeneous distribution of biomaterials in plaques which include proteins, lipids, calcium and blood products. Currently, the proton signal from macromolecules is unobservable in conventional in vivo imaging and spectroscopy. The investigators propose in this application the development and optimization of magnetization transfer contrast (MTC) that is a sensitive indicator of the presence of rationally immobilized macromolecule, and therefore, optimum for detection of a fibrous cap in atheroma. Previous studies suggest that the vulnerable lesion is one composed of a thin fibrous cap surrounding a large lipid pool. The dependence of the water signal on the frequency of the magnetization transfer preparation pulse forms a cross-relaxation profile that reveals the linewidth the lineshape of the MR invisible macromolecule enabling identification of variations within the cap that will signal regions of inflammatory response, and thus susceptibility to rupture. Additionally, the motional dynamics of the lipids in the atheromatous gruel are also measured through magnetic cross-relaxation to the surrounding water protons. Development of the MR techniques for resolving the vulnerable atherosclerotic plaque components will be achieved by the following: 1) In lipid and protein phantoms that model the major components of atheroma, characterize the biophysical mechanism of magnetization transfer (MT under various conditions, 2) In excised human arteries directly detect with high resolution NMR microimaging and spectroscopy at 9.4 T the solid, semi-solid, and liquid components as well as their inter-molecular magnetic cross-relaxation and individual relaxation rates to establish how these relate to plaque characteristics such as staging and presence of inflammatory response. 3) Develop in vivo atherosclerotic vascular imaging at 3 Tesla using optimized MR sequences. Examine carotid artery atheromas in patients scheduled for carotid endarterectomy, and examine atherectomy specimens for plaque morphometrics and immunohistochemistry. They will also develop novel methods for evaluating in situ plaque calcification to determine the chemical composition of the calcium phosphate.